Explanation of trial sequential analysis: Using a post-hoc analysis of meta-analyses published in Korean journal of anesthesiology

Abstract

Background: Trial sequential analysis (TSA) is a recent cumulative meta-analysis method used to weigh type I and II errors and to estimate when the effect is large enough to be un-affected by further studies. The aim of this study was to illustrate possible TSA scenarios and their significance using meta-analyses published in the Korean Journal of Anesthesiology (KJA) as working material. Methods: We performed a systematic medical literature search for meta-analyses published in the KJA. TSA was performed on each main outcome, estimating the required sample size on the calculated effect size for the intervention, considering a type I error of 5% and a power of 90% or 99%. Results: Six meta-analyses with a total of ten main outcomes were included in the analysis. Seven TSAs confirmed the results of the meta-analyses. However, only three of them reached the required sample size. In the two TSAs, the cumulative z-lines were not statisti-cally significant. One TSA boundary for effect was reached with the 90% analysis, but not with the 99% analysis. Conclusions: In TSA, a meta-analysis pooled effect may be established to assess if the cumulative sample size is large enough. TSA can be used to add strength to the conclusions of meta-analyses; however, pre-registration of the TSA protocol is of paramount impor-tance. This study could be useful to better understand the use of TSA as an additional statistical tool to improve meta-analysis quality.